1333041 - Accelerated vascular stiffening in premenopausal women undergoing breast cancer treatment: Insights from the PREVENT Trial (WF-98213)

Systemic therapies which improve outcomes in breast cancer (BC) also carry cardiovascular (CV) risk which may offset survival gains. While anthracycline-induced CV toxicity is well known, there is emerging data that premenopausal women with hormone receptor positive (HR+) BC treated with near complete estrogen deprivation may experience treatment-related CV injury [1]. In premenopausal women with triple negative BC (TNBC), chemotherapy-induced cessation of menses may also alter normally pliable aortic stiffness measures. Thus, we investigated the 2-year change in vascular stiffness using cardiovascular magnetic resonance (CMR) imaging from the PREVENT Trial (NCT01988571, R01HL118740)[2] including sub-analyses by BC subtype and menopausal status to study the impact of cancer therapy and menopausal status on vascular stiffness.

Methods:

238 BC patients were randomized to two years of 40 mg daily atorvastatin or placebo.  BC patients underwent baseline CMRs prior to initiation of anthracycline-based treatment and at 6 and 24 months.  The study was conducted at 31 NCI-funded NCORP Research Cooperative sites through the Wake Forest NCORP Research Base (2UG1CA189824). Each CMR used established measures of 2D aortic pulse wave velocity (PWV) and both ascending and descending aortic distensibility (AoD) [3]. Least squares means were estimated using longitudinal general linear mixed models for each outcome after adjustments for baseline value, hypertension, body mass index, statin treatment group, BC disease subtype, and menopausal status with a two-way interaction for time with both BC diagnosis and menopausal status.

Results:

A total of 116 (65% HR+, 35% TNBC) premenopausal and 122 (58% HR+, 42% TNBC) postmenopausal BC patients were included (Table 1). Baseline PWV was not different between disease groups but was markedly increased in the TNBC group at 24 months (Panel A, p=0002). At baseline, PWV was increased in post-menopausal women compared to pre-menopausal women (Panel B, p< 0.01). By 24 months, PWV increased in pre-menopausal women and surpassed the PWV of post-menopausal women. All subgroups had significant 24-month declines in both ascending and descending AoD (Panels C-F). No models demonstrated an effect of atorvastatin on aortic stiffness measures.

Conclusion: In women treated for BC with anthracycline-based chemotherapy, CMR aortic stiffness measures demonstrate global stiffening. While pre-menopausal women had compliant aortic vessels prior to cancer treatment, at two years aortic vessels were either equivalent or worse than aortas of post-menopausal women. In summary, our trial demonstrated that women with TNBC and premenopausal women experience  more aortic stiffening related to anthracycline-treated chemotherapy and may represent higher risk groups in which increased cardiac monitoring or intervention may be beneficial.